Oxidative stress is thought to be a major contributor to the development of retinal degenerative disorders such as macular degeneration, retinopathy of prematurity and diabetic retinopathy. In order to understand the mechanism(s) of oxidative damage to the retina, we have investigated the gene expression in the retina of rats exposed to intense visible light. In the past, we have shown that the expression of heme oxygenase (HO-1) mRNA in the retina is markedly increased in response to acute intense light exposure. The increase in HO-1 mRNA, a marker for oxidative stress, is dependent on factors such as age, light history and antioxidant status. In the current investigation, we examined whether the retinal light damage in rats is dependent on circadian rhythm. The susceptibility to light damage as indicated by the increased expression of HO-1 mRNA was highest when light exposure was initiated at 0100 h. In contrast, the light damage was very minimal when light exposure was initiated during the period of 1500-1700 h. Thus, the intense visible light exposure during the night time phase of the diurnal cycle is more injurious to retina than that administered during the day time. The increase in HO-1 mRNA was associated with the loss of photoreceptor cells as indicated by the appearance of apoptotic DNA ladders and a decrease in the level of mRNA for interphotoreceptor retinol binding protein (IRBP). Our results indicate that certain factor(s) that are present in retina and regulated by circadian rhythm could modulate its response to light damage.